Reversal of human neutrophil survival by leukotriene B(4) receptor blockade and 5-lipoxygenase and 5-lipoxygenase activating protein inhibitors

American Journal of Respiratory and Critical Care Medicine
E LeeS Kilfeather


Persistent neutrophilia is a feature of chronic obstructive pulmonary disease (COPD). Leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists have shown efficacy in the treatment of asthma. Antagonism of leukotriene (LT)B(4) receptors is being considered as a mode of treating COPD. We examined the capacity for inhibition of leukotriene synthesis and LTB(4) receptor antagonism to reduce survival of neutrophils from patients with COPD and those from normal subjects. The basal apoptosis level of these cells was 55.4 +/- 2.4% (mean +/- SEM) of total cells. Separate exposure to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), dexamethasone (DEX), and LTB(4) increased neutrophil survival (p < 0. 001). The LTB(4) receptor antagonist SB201146 abolished LPS-induced survival in a concentration-dependent manner (10 pmol to 0.1 microM), with an IC(50) of 1.9 nM. Combined exposure to SB201146 and to the cysteinyl leukotriene antagonist SKF104353 did not have a greater effect on survival than did exposure to SB201146 alone. Inhibition of 5-lipoxygenase (5-LO) with BWA4C and of 5-LO-activating protein (FLAP) with MK886 abolished GM-CSF- and DEX-induced neutrophil survival. BWA4C and ...Continue Reading


Apr 1, 1992·International Journal of Immunopharmacology·H E ClaessonP J Jakobsson
Jan 1, 1991·Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum·P N Bouchelouche, D Berild
Dec 1, 1989·The American Review of Respiratory Disease·A B ThompsonS I Rennard
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·D G TangK V Honn
Oct 31, 1996·Experientia·S P HartI Dransfield
Mar 1, 1997·Chest·C E McEvoy, D E Niewoehner
Mar 28, 1998·American Journal of Respiratory and Critical Care Medicine·B W LeeD C Christiani
Jun 3, 1998·The International Journal of Biochemistry & Cell Biology·S W Crooks, R A Stockley
Jul 31, 1998·Clinical Science·A M CondliffeE R Chilvers

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